Silence Therapeutics plc (AIM: SLN) ("Silence" or the "Company"), a leading global RNA interference (RNAi) therapeutics company, on Monday presented the latest data from its ongoing Phase I study of Atu027, its lead internal therapeutics candidate, alongside the 2012 American Society of Clinical Oncology ("ASCO") Annual Meeting in Chicago, Illinois. At this meeting, Klaus Giese, Ph.D., Silence's Chief Scientific Officer and the study's principal investigator Dr. Dirk Strumberg, Professor of Medicine and Director of Department of Hematology and Medical Oncology at University of Bochum (Marienhospital Herne, Germany), gave an update and discussed the data from the Atu027 Phase I trial.

Silence's open label, single-centre, dose-finding Phase I study of Atu027 in subjects with advanced solid cancer was designed to evaluate up to a total of 11 escalating doses of Atu027. The enrolment of patients in the last cohort in dose level 10 has been completed and last treatment is scheduled on 22nd of June 2012. Atu027 was very well tolerated and safe up to the 10th dose level. No premedication was needed in support of Atu027 treatment. The prospective recommended maximum tolerated dose is 0.336 mg/kg. "Stable disease" response for three and six months after treatment was observed in 10 and 3 patients, respectively, of the 33 evaluable patients. Two patients with neuroendocrine cancer had disease stabilisation for 9 and 12 months. Partial regression of pulmonary metastases was found in another patient. A further patient with breast cancer showed regression of liver metastases.

Further evaluation showed that treatment with Atu027 at dose level 8 (0.18 mg siRNA/kg) achieved the same blood plasma siRNA concentration that in preclinical studies had been sufficient to trigger silencing of PKN3 expression. Therefore, the tested dose levels 8-10 can be considered effective and safe. These data are supported by the identification of a putative biomarker. Reduction of soluble VEGF-R1 (sFLT-1) levels was observed in plasma samples from 7 out of 9 patients in dose levels 6-9 after repeated Atu027 treatment. Interestingly, the levels of soluble VEGF-R2 and soluble VEGF-R3 were not changed upon Atu027 treatment. There is evidence that sVEGF-R1 function could be a direct downstream effector of PKN3 and as such serve as a readout for biological activity.

Silence also announces that it is in advanced discussions to raise between £4-5m from new and existing shareholders to secure the funding for the Company's R&D and marketing through until 2014.

Klaus Giese, Chief Scientific Officer of Silence, commented: "These are very encouraging results. We believe that PKN3 is central to the signaling pathway critical for steering cancer metastasis. The reported anti-metastatic activity, safety and tolerability of Atu027 in patients advocate for future testing of Atu027 combination therapy with existing chemotherapeutic regimens. This Phase I study has laid the foundation for a novel RNAi therapeutic as a promising treatment option for cancer patients."

Silence Therapeutics plc (AIM: SLN) is a leading biotechnology company dedicated to the discovery, development and delivery of targeted, systemic RNA interference (RNAi) therapeutics for the treatment of serious diseases. Silence offers one of the most comprehensive short interfering RNA (siRNA) therapeutic platforms available today based on a strong intellectual property portfolio and large clinical safety database. Silence's clinical siRNA product pipeline is one of the broadest in the industry. The Company possesses multiple proprietary siRNA delivery technology platforms including AtuPLEX™, DACC and DBTC. AtuPLEX enables the broad functional delivery of siRNA molecules to targeted diseased tissues and cells, while increasing their bioavailability and intracellular uptake. The DACC delivery system allows functional delivery of siRNA molecules selectively to the lung endothelium with a long duration of target mRNA and protein knock-down. The DBTC delivery system enables functional delivery of siRNA molecules selectively to liver cells including hepatocytes. Additionally, the Company has a platform of novel siRNA molecules based around its AtuRNAi chemical modification technology, which provides a number of advantages over conventional siRNA molecules. Silence's unique RNAi assets also include structural features for RNAi molecules and specific design rules for increased potency and reduced off-target effects of siRNA sequences.

The Company's lead internal drug candidate is Atu027, a liposomal formulation in clinical development for systemic cancer indications and one of the most clinically advanced RNAi therapeutic candidates in the area of oncology. Atu027 incorporates two of the Company's technologies, AtuRNAi and AtuPLEX™. Silence is currently conducting an open-label, single-centre, dose-escalation Phase I study with Atu027 in patients with advanced solid tumors involving single, as well as repeated, intravenous administration. Encouraging interim safety and pharmacokinetic data were presented at the American Society of Clinical Oncology Annual Meeting in June 2011. The study is expected to be completed in July 2012.

The Company's RNAi therapeutic platform has received key validation through multiple partnerships with pharmaceutical companies including AstraZeneca, Dainippon Sumitomo, Pfizer/Quark, and Novartis/Quark. Silence is actively pursuing the establishment of additional partnerships. Silence Therapeutics has operations in both Berlin and London.